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Facile immobilization is essential for the wide application of enzymes in large-scale catalytic processes. However, exploration of suitable enzyme supports poses an unmet challenge, particularly in the context of scale-up biocatalyst fabrication. In this study, we present facile and scale-up syntheses of high-performance enzyme biocatalysts via in situ encapsulation of cytochrome c (Cyt-c) as mono-enzyme and glucose oxidase (GOx)-horseradish peroxidase (HRP) as dual-enzyme cascade (GOx&HRP) systems, respectively, into a stable mesoporous hydrogen-bonded organic framework (meso-HOF) matrix. In situ encapsulation reactions occur under ambient conditions, and facilitate scale up (â¼3 g per reaction) of enzyme@meso-HOF within a very short period (5-10 min). The resultant biocatalysts not only exhibit high enzyme loading (37.9 wt% for mono-enzyme and 22.8 wt% for dual-enzyme) with minimal leaching, but also demonstrate high catalytic activity, superior reusability, and durability. This study represents an example of scale-up fabrication of enzyme@meso-HOF biocatalysts on the gram level and highlights superior meso-HOFs as suitable host matrices for biomolecular entities.
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Understanding and predicting interface diffusion phenomena in materials is crucial for various industrial applications, including semiconductor manufacturing, battery technology, and catalysis. In this study, we propose a novel approach utilizing Graph Neural Networks (GNNs) to investigate and model material interface diffusion. We begin by collecting experimental and simulated data on diffusion coefficients, concentration gradients, and other relevant parameters from diverse material systems. The data are preprocessed, and key features influencing interface diffusion are extracted. Subsequently, we construct a GNN model tailored to the diffusion problem, with a graph representation capturing the atomic structure of materials. The model architecture includes multiple graph convolutional layers for feature aggregation and update, as well as optional graph attention layers to capture complex relationships between atoms. We train and validate the GNN model using the preprocessed data, achieving accurate predictions of diffusion coefficients, diffusion rates, concentration profiles, and potential diffusion pathways. Our approach offers insights into the underlying mechanisms of interface diffusion and provides a valuable tool for optimizing material design and engineering. Additionally, our method offers possible strategies to solve the longstanding problems related to materials interface diffusion.
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In this editorial, we comment on the article by Zhou et al published in a recent issue. We specifically focus on the crucial roles of ferroptosis and pyroptosis in acute liver failure (ALF), a disease with high mortality rates. Ferroptosis is the result of increased intracellular reactive oxygen species due to iron accumulation, glutathione (GSH) depletion, and decreased GSH peroxidase 4 activity, while pyroptosis is a procedural cell death mediated by gasdermin D which initiates a sustained inflammatory process. In this review, we describe the characteristics of ferroptosis and pyroptosis, and discuss the involvement of the two cell death modes in the onset and development of ALF. Furthermore, we summarize several interfering methods from the perspective of ferroptosis and pyroptosis for the alleviation of ALF. These observations might provide new targets and a theoretical basis for the treatment of ALF, which are also crucial for improving the prognosis of patients with ALF.
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Ferroptose , Falência Hepática Aguda , Piroptose , Espécies Reativas de Oxigênio , Humanos , Falência Hepática Aguda/patologia , Falência Hepática Aguda/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ferro/metabolismo , Animais , Glutationa/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Fígado/patologia , Fígado/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Prognóstico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , GasderminasRESUMO
Stage I non-small cell lung cancer (NSCLC) accounts for about 15% of incident cancer cases. Prognosis is poor, with a metastasis and recurrence rate of 38% within 2 years of surgery and an overall 5-year survival rate of 54-60%. Here, we report successful apatinib monotherapy of early NSCLC in a patient who had declined surgery, radiofrequency ablation, and immunotherapy. The patient received apatinib for 64 months without clinical, laboratory, or radiographic evidence of disease progression. The curative effect was judged to be stable and safe.The role of apatinib as monotherapy for patients with early stage NSCLC who are not candidates for surgery or radiotherapy, or as an adjunct to standard therapy, deserves further study.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piridinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Masculino , Estadiamento de Neoplasias , Idoso , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Temporary hemiepiphysiodesis (TH) is a very common technique for coronal angular deformity of the knee in children, especially non-idiopathic. However, there is currently a dearth of comparative research on the hinge eight-plate (HEP) and traditional eight-plate (TEP). This study aimed to assess the clinical effectiveness and implant-related complication rates of TH using TEP and HEP for non-idiopathic coronal angular deformity, as well as to identify clinical factors affecting correction velocity. METHODS: We retrospectively observed a consecutive series of patients with non-idiopathic coronal angular deformity of the knee who underwent TH using HEP or TEP and completed the deformity correction process from July 2016 to July 2022. According to the kind of eight plates, we divided those patients into the HEP group and the TEP treatment group. Relevant clinical factors, including the mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), screw divergence angle (SDA), angle of plate and screw (APS), hinge angle of HEP (HA), and the knee zone location of the lower extremity mechanical axis, were documented. Additionally, deformity correction velocity, complications, and clinical efficacy were assessed. Categorical variables were analyzed using the chi-squared test, Fisher exact test, or Wilcoxon test, while continuous variables were evaluated using the t-test or analysis of variance (ANOVA). RESULTS: There were 29 patients in the HEP treatment group (seven girls and 22 boys) and 33 patients (12 girls and 21 boys) in the TEP treatment group. In all, 91.86% (79/86 knees) of the genu angular deformities were completely corrected, 6.98% (6/86 knees) had the overcorrection condition, and 10.47% (9/86 knees) had screw loosening. The swayback HEP rate was 11.29% (7/62 HEPs), which was related to the screw loosening in the HEP group (p < 0.001). The overall correction velocities and screw divergence angle change speeds in the HEP group were all significantly faster than those in the TEP group (p < 0.05). The initial APS of the HEP implanted was higher than that of TEP (p < 0.01), and multisite changes of APS during deformity correction of the HEP group were smaller than that of the TEP group. CONCLUSION: HEP proved to be an appropriate device for TH for non-idiopathic coronal angular deformities of the knee with high correction velocity in children. Avoiding the occurrence of the swayback phenomenon may reduce the complications of HEP.
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Balancing optical modulation and response time is crucial for achieving high coloration efficiency in electrochromic materials. Here, internal electric fields are introduced to titanium dioxide nanosheets by constructing abundant amorphous-crystalline interfaces, ensuring large optical modulation while reducing response time and therefore improving coloration efficiency. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) reveals the presence of numerous amorphous-crystalline phase boundaries in titanium dioxide nanosheets. Kelvin probe force microscopy (KPFM) exhibits an intense surface potential distribution, demonstrating the presence of internal electric fields. Density functional theory (DFT) calculations confirm that the amorphous-crystalline heterointerfaces can generate internal electric fields and reduce diffusion barriers of lithium ions. As a result, the amorphous-crystalline titanium dioxide nanosheets exhibit better coloration efficiency (35.1 cm2 C-1) than pure amorphous and crystalline titanium dioxide nanosheets.
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The experimental demonstration of a p-type 2D WSe2 transistor with a ferroelectric perovskite BaTiO3 gate oxide is presented. The 30 nm thick BaTiO3 gate stack shows a robust ferroelectric hysteresis with a remanent polarization of 20 µC/cm2 and further enables a capacitance equivalent thickness of 0.5 nm in the hybrid WSe2/BaTiO3 stack due to its high dielectric constant of 323. We demonstrate one of the best ON currents for perovskite gate 2D transistors in the literature. This is enabled by high-quality epitaxial growth of BaTiO3 and a single 2D layer transfer based fabrication method that is shown to be amenable to silicon platforms. This demonstration is an important milestone toward the integration of crystalline complex oxides with 2D channel materials for scaled CMOS and low-voltage ferroelectric logic applications.
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Sucrose is a commonly utilized nutritive sweetener in food and beverages due to its abundance in nature and low production costs. However, excessive intake of sucrose increases the risk of metabolic disorders, including diabetes and obesity. Therefore, there is a growing demand for the development of nonnutritive sweeteners with almost no calories. d-Allulose is an ultra-low-calorie, rare six-carbon monosaccharide with high sweetness, making it an ideal alternative to sucrose. In this study, we developed a cell factory for d-allulose production from sucrose using Escherichia coli JM109 (DE3) as a chassis host. The genes cscA, cscB, cscK, alsE, and a6PP were co-expressed for the construction of the synthesis pathway. Then, the introduction of ptsG-F and knockout of ptsG, fruA, ptsI, and ptsH to reprogram sugar transport pathways resulted in an improvement in substrate utilization. Next, the carbon fluxes of the Embden-Meyerhof-Parnas and the pentose phosphate pathways were regulated by the inactivation of pfkA and zwf, achieving an increase in d-allulose titer and yield of 154.2% and 161.1%, respectively. Finally, scaled-up fermentation was performed in a 5 L fermenter. The titer of d-allulose reached 11.15 g/L, with a yield of 0.208 g/g on sucrose.
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BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Receptores Imunológicos , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Masculino , Feminino , Prognóstico , Receptores Imunológicos/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos , Quimioembolização Terapêutica/métodos , Idoso , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto , Receptores Virais/metabolismoRESUMO
The prevalence of frailty is increasing, and it is associated with increased risk of diseases and adverse outcomes. Although substantial research has focused on post-stroke frailty, understanding of pre-stroke frailty remains limited. Our aim was to synthesize literature on pre-stroke frailty and stroke risk to explore their relationship and impact on prognosis. A systematic search of multiple databases was conducted to identify cohort studies published until October 28, 2023. Meta-analysis was conducted using a random effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated using Begg's test. Finally, we included 11 studies (n = 1,660,328 participants). The pooled hazard ratios (HRs) for stroke risk associated with pre-stroke frailty compared to non-frail individuals was 1.72 (95% confidence interval, CI: 1.46-2.02, p = 0.002, I2 = 69.2%, Begg's test: p = 0.536). The pooled HRs for mortality and the pooled relative risk (RRs) modified Rankin Scale (mRs) associated with pre-stroke frailty were 1.68 (95% CI: 1.10-2.56, p = 0.136, I2 = 49.9%, Begg's test: p = 0.296) and 3.11 (95% CI: 1.77-5.46, p = 0.192, I2 = 39.4%, Begg's test: p = 1.000), respectively. In conclusion, pre-stroke frailty is strongly associated with stroke risk and impacts its prognosis, irrespective of the measurement method. Future research should focus on prospective studies to assess the effects of early intervention for frailty. This has significant implications for primary healthcare services and frailty management.
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Fragilidade , Acidente Vascular Cerebral , Idoso , Humanos , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/complicações , Fragilidade/epidemiologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Diabetes mellitus type 2 (T2DM) is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action. It has been affecting over 400 million people all over the world. AIM: To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM. METHODS: Receiver operating characteristic (ROC) curve analysis was used to conduct diagnostic markers. The expression level of genes was determined by reverse transcription-PCR as well as Western blot. Cell proliferation assays were performed by cell counting kit-8 (CCK-8) tests. At last, T2DM mice underwent Roux-en-Y gastric bypass surgery. RESULTS: We found that NPAS2 was significantly up-regulated in islet ß cell apoptosis of T2DM. The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM. NPAS2 overexpression did increase the level of KANK1. In addition, the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells. At last, we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1. CONCLUSION: This study demonstrated that NPAS2 induced ß cell dysfunction by regulating KANK1 expression in type 2 diabetes, and it may be an underlying therapy target of T2DM.
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Arecoline (ACL), an active constituent derived from Areca catechu L., exerts various pharmacological effects and serves as a potential plant-based insecticide. However, the effects of ACL on Spodoptera litura, an important and widely distributed agricultural pest, remain unknown. This study aimed to elucidate the mechanism underlying ACL-induced toxicity and its inhibitory effects on larval growth and development through intestinal pathology observations, intestinal transcriptome sequencing, intestinal digestive enzyme activity analysis. The results indicated that ACL exposure leads to pathological alterations in the S. litura midgut. Furthermore, the detection of digestive enzyme activity revealed that ACL inhibits the activities of acetyl CoA carboxylase, lipase, α-amylase, and trypsin. Simultaneously, upregulation of superoxide dismutase activity and downregulation of malondialdehyde levels were observed after ACL exposure. Transcriptome analysis identified 1118 genes that were significantly differentially expressed in the midgut after ACL exposure, potentially related to ACL toxic effects. Notably, ACL treatment downregulated key enzymes involved in lipid metabolism, such as fatty acid binding protein 2-like, pancreatic triacylglycerol lipase-like, pancreatic lipid-related protein 2-like, and fatty acid binding protein 1-like. Taken together, these results suggest that ACL induces midgut damage and impedes larval growth by suppressing digestive enzyme activity in the intestine. These findings can aid in the development of environmentally friendly plant-derived insecticides, utilizing ACL to effectively combat S. litura proliferation.
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Intestinos , Larva , Spodoptera , Animais , Spodoptera/efeitos dos fármacos , Spodoptera/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Inseticidas/toxicidade , Inseticidas/farmacologia , Lipase/metabolismo , Lipase/genéticaRESUMO
Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.
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Methicillin-resistant Staphylococcus aureus (MRSA) is rapidly spreading worldwide, emerging as a leading cause of bacterial infections in healthcare and community settings. This poses serious risks to human health. The shortage of novel antibiotics and the absence of effective vaccines make MRSA particularly challenging to treat. Existing vaccine development strategies often fail to provide early protection against infections, highlighting the urgent need for solutions. Herein, we propose a novel strategy combining trained immunity with a multi-epitope subunit vaccine to combat MRSA infections. We comprehensively evaluated the trained immune phenotypes induced by ß-glucan from barley and curdlan. Macrophages trained with curdlan exhibited a more balanced inflammatory response compared to ß-glucan from barley, expressing higher levels of IL-1ß, IFN-ß, TGF-ß, and CCL2 upon secondary stimulation. Furthermore, curdlan-induced trained immunity rapidly provided excellent protection against S. aureus infection in mice. RNA-sequencing analysis revealed that curdlan modulates the Wnt signaling pathway in macrophages, resolves inflammation, and promotes tissue repair. When combined with one or two doses of S. aureus multivalent epitope antigen against MRSA infection, curdlan-induced trained immunity enhanced early protection and promoted recovery. Our study demonstrates the feasibility of combining trained immunity with vaccine protection against MRSA, providing a strategy against multi-drug resistant bacteria.
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A lack of access to handwashing facilities is a significant risk factor for lower respiratory infections(LRIs). However, no studies have reported epidemiologic changes in the burden of LRIs attributed to the lack of access to handwashing facilities. We conducted an integrated assessment of the burden of LRIs attributable to the lack of handwashing facilities from 1990 to 2019 using data from the Global Burden of Disease Study 2019. In 2019, 270,000 deaths were attributed to LRIs due to a lack of access to handwashing facilities, with DALYs reaching 14.02 million. The age-standardized mortality rate (ASMR) of LRIs caused by a lack of access to handwashing facilities was approximately 3.74, while the age-standardized DALY rate (ASDR) was reported to be 203.55 in 2019. Over the past 30 years, the burden of LRIs attributed to the lack of access to handwashing facilities has shown a global decline. In 2019, this burden was most pronounced in infants under 1 year of age and in those older than 95 years, reflecting the highest DALY (5591.83) and mortality rates (79.43), respectively. The burden of LRIs caused by the lack of access to handwashing facilities was found to be more severe in males and significantly more pronounced in regions with a low sociodemographic index (SDI), such as the Sahara African region. The development of targeted strategies to address the inadequate and unequal distribution of handwashing facilities holds important value in improving the disease burden of LRIs.
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INTRODUCTION: The aim of this study was to evaluate the utility of 2D-STI and real-time three-dimensional echocardiography (RT-3DE) in assessing changes in left atrial (LA) structure and function in patients with paroxysmal atrial fibrillation (PAF) post-radiofrequency catheter ablation (RFCA). METHODS: A retrospective analysis was conducted on 44 PAF patients who underwent RFCA at BA Hospital from March 2022 to March 2023. An age- and gender-matched control group of 32 healthy individuals was also included. Comprehensive echocardiographic parameters including LA dimensions (LAAPD, LALRD), volumes (LAVmin, LAVmax), ejection fraction (LAEF), and tissue velocities (a', Ar) were compared between groups. Post-RFCA changes in these parameters were also assessed at 1, 3, and 6 months. RESULTS: Pre-RFCA, PAF patients demonstrated larger LA dimensions and volumes with reduced LAEF and tissue velocities compared to controls. Post-RFCA, there was a significant improvement in LAEF and left ventricular ejection fraction at 1, 3, and 6 months, with the most pronounced changes observed at 6 months. LA dimensions increased initially but then decreased from 1 to 6 months post-RFCA. Notably, strain rate (SRS, SRE, SRA) measurements in various LA segments improved progressively, with the most significant enhancements at 6 months, suggesting improved atrial mechanics. CONCLUSION: The application of 2D-STI and RT-3DE provides a quantitative means to evaluate the structural and functional changes in the LA of PAF patients following RFCA. The progressive improvements in LA dimensions, volumes, and strain measurements up to 6-month post-RFCA indicate the potential of these techniques in monitoring treatment efficacy and patient recovery.
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BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of some chemotherapeutic agents. Effective treatment is limited. OBJECTIVES: This single patient case details gua sha as an intervention to reduce CIPN. METHODS: A 38-year-old female patient received weekly treatment of gua sha in one-hour sessions for 10 weeks. The patient completed the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale to describe her CIPN throughout and postintervention. A research assistant measured the extent of numbness or tingling along the limb from baseline to 18 months after gua sha. Descriptive data were used to summarize this case. FINDINGS: After gua sha, the total FACT/GOG-NTX subscale score increased from 13 to 36, indicating a sevenfold greater change than the minimum clinically important difference. The range of limb numbness and tingling decreased, and the symptoms remained stable during follow-up. Gua sha showed a positive clinical effect.
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Antineoplásicos , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Adulto , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/terapia , Antineoplásicos/efeitos adversosRESUMO
BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.
Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.
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Escores de Disfunção Orgânica , Curva ROC , Humanos , Masculino , Feminino , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Pneumonia/mortalidade , Pneumonia/diagnóstico , Índice de Gravidade de Doença , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/diagnóstico , Sepse/mortalidade , Sepse/diagnóstico , Taxa Respiratória , Idoso de 80 Anos ou mais , Pressão Sanguínea , Valor Preditivo dos Testes , PrognósticoRESUMO
L-Threonine aldolase (L-TA) is a pyridoxal phosphate-dependent enzyme that catalyzes the reversible condensation of glycine and aldehydes to form ß-hydroxy-α-amino acids. The combination of directed evolution and efficient high-throughput screening methods is an effective strategy for enhancing the enzyme's catalytic performance. However, few feasible high-throughput methods exist for engineering the Cß-stereoselectivity of L-TAs. Here, we present a novel method of screening for variants with improved Cß-stereoselectivity; this method couples an L-threo-phenylserine dehydrogenase, which catalyzes the specific oxidation of L-threo-4-methylsulfonylphenylserine (L-threo-MTPS), with the concurrent synthesis of NADPH, which is easily detectable via 340-nm UV absorption. This enables the visual detection of L-threo-MTPS produced by L-TA through the measurement of generated NADPH. Using this method, we discover an L-TA variant with significantly higher diastereoselectivity, increasing from 0.98% de (for the wild-type) to 71.9% de.
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Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cancer cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in cancer progression. The review begins with a detailed exposition on the origins of TAMs and their functional heterogeneity, providing a foundational understanding of TAM characteristics. Next, it delves into the specific molecular mechanisms through which TAMs induce EMT, including cytokines, chemokines and stromal cross-talking. Following this, the review explores TAM-induced EMT features in select cancer types with notable EMT characteristics, highlighting recent insights and the impact of TAMs on cancer progression. Finally, the review concludes with a discussion of potential therapeutic targets and strategies aimed at mitigating TAM infiltration and disrupting the EMT signaling network, thereby underscoring the potential of emerging treatments to combat TAM-mediated EMT in cancer. This comprehensive analysis reaffirms the necessity for continued exploration into TAMs' regulatory roles within cancer biology to refine therapeutic approaches and improve patient outcomes.